Alloreactivity of an antigen-specific T-cell clone

Abstract

The apparent high frequency of alloreactive T cells has suggested that the two subpopulations—T cells specific for soluble protein antigens and alloreactive T cells—must overlap^1–3. However, the existence of a set of germ-line genes encoding a family of anti-MHC (major histocompatibility complex) antigen-specific T-cell receptors has also been postulated to explain the high frequency of alloreactive clones^4–7. In these latter models the two T-cell subpopulations are viewed as separate. Studies on whole T-cell populations have examined these two points of view by looking for cross-stimulation of alloreactive cells with antigen and vice versa^8–11. Although significant cross-reactions have been reported, the problem of nonspecific recruitment made interpretation of results difficult. Recent developments in the cloning of antigen-specific T lymphocytes^12–18 have finally allowed investigation at the single-cell level where the results should be unambiguous, von Boehmer et al.¹⁴ have isolated a cytotoxic clone specific for the H–Y antigen in conjunction with the syngeneic MHC antigens coded for by D^b. This clone was also cytotoxic for spleen cells bearing the alloantigens coded for by D^d in the absence of the H–Y antigen. However, because cytotoxic clones only grow in the presence of T-cell growth factor (TCGF) and because von Boehmer et al. were unable to stimulate or enrich for D^d-specific cytotoxic activity from bulk cultures initially stimulated with H–Y and D^b-bearing spleen cells¹⁴, they hesitate to conclude that the same cell can respond to both foreign and alloantigens. We show here that a (dinitrophenyl-ovalbumin)(DNP-OVA)-specific T-cell clone from a B10.A mouse can be stimulated to divide (and propagate) in vitro with B10.S allogeneic spleen cells in the absence of DNP-OVA and B10.A antigen-presenting cells. Extensive recloning strongly suggests that a single T-cell clone is responding to two separate stimuli, a specific alloantigen and a soluble antigen in conjunction with self-MHC products.